No abstract

Group B streptococcus (GBS) or Streptococcus agalactiae, is an opportunistic pathogen causing a wide range of infections like pneumonia, sepsis, and meningitis in newborn, pregnant women and adults. While this bacterium has adapted well to asymptomatic colonization of adult humans, it still remains a potentially devastating pathogen to susceptible infants. Advances in molecular techniques and refinement of in vitro and in vivo model systems have elucidated key elements of the pathogenic process, from initial attachment to the maternal vaginal epithelium to penetration of the newborn blood-brain barrier. Still, the formidable array of GBS virulence factors makes this bacterium at the forefront of neonatal pathogens. The involvement of bacterial components in the host-pathogen interaction of GBS pathogenesis and its related diseases is not clearly understood. In this study we demonstrated the role of a 39 kDa factor from GBS which plays an important role in the process of its invasion. We found a homogeneous 39 kDa factor from the cytosol of GBS after following a combination of sequential purification steps involving molecular sieving and ion exchange chromatography using ACTA-FPLC system. Its N-terminal sequence showed a homology with xenobiotic response element type transcriptional regulator protein, a 40 kDa protein of Streptococcus. This factor leads to inhibition of GBS invasion in HeLa and A549 cells. This protein also showed sensitivity and specific cross reactivity with the antibodies raised against it in New Zealand white rabbits by western immunoblotting. This inhibitory factor was further confirmed tolerant for its cytotoxicity. These results add a novel aspect to bacterial pathogenesis where bacteria's own intracellular protein component can act as a potential therapeutic candidate by decreasing the severity of disease thus promoting its invasion inhibition.

Acute myeloid leukaemia (AML) is a highly heterogeneous disorder and is characterised by the proliferation of poorly differentiated myeloid cells due to underlying mutation, eventually causing bone marrow failure. Accounting for approximately 25% of cases, AML is the most frequent form of leukaemia in the world yet has the lowest survival rate among all leukaemias. Patients with haematological malignancy are more susceptible to severe acute respiratory syndrome coronavirus-2 infection and further development of severe infection, including pneumonia with poor blood oxygenation. The management of such patients is more challenging than expected. Successful management of one such case is discussed in this report. COVID-19 infection can cause great harm to a patient with underlying leukaemia and increase the mortality risk. It has a major impact on the physical and psychological health of the patient. Therefore, these patients need special care and attention. The authors emphasise the importance of supportive management (oxygen with bilevel positive airway pressure, prone positioning, and physiotherapy) to prevent complications.

Falciparum malaria is one of the most common causes of acute febrile illness in India and frequently presents as severe malaria also known as complicated malaria or cerebral malaria with associated multiple organ failure. Acute pancreatitis secondary to malaria is very rare complication. Here we are presenting a case of severe falciparum malaria with acute pancreatitis.

Purpose Definitive antiviral treatment is not available for COVID-19 infection, with the exception of remdesivir, which still evokes many doubts. Various monotherapy or combination therapies with antivirals or other agents have been tried. The present study aims to evaluate the therapeutic potential of hydroxychloroquine and lopinavir–ritonavir in combination with ribavirin in mild–severe COVID-19. Patients and Methods A single-center, open-label, parallel-arm, stratified randomized controlled trial evaluated the therapeutic potential of combination antiviral therapies. Enrolled patients in the severe category were randomized into three groups: (A) standard treatment, (B) hydroxychloroquine+ribavirin+standard treatment, or (C) lopinavir+ritonavir+ribavirin+standard treatment; while the non-severe category comprised two groups: (A) standard treatment or (B) hydroxychloroquine+ribavirin. Combination antivirals were given for 10 days and followed for 28 days. The primary endpoints were safety, symptomatic and laboratory recovery of organ dysfunctions, and time to SARS-CoV-2 RT-PCR negative report. Results In total, 111 patients were randomized: 24, 23, and 24 in severe categories A, B, and C, respectively, and 20 in each of the non-severe groups. Two patients receiving ribavirin experienced drug induced liver injury, and another developed QT prolongation after hydroxychloroquine. In the severe category, 47.6%, 55%, and 30.09% in A, B, and C groups, respectively, showed symptomatic recovery, compared to 93.3% and 86.7% in A and B groups, respectively, in the non-severe category at 72 hours ( P >0.05). Conclusion Though the results failed to show statistical superiority of the antiviral combination therapies to that of the standard therapy in both the severe and non-severe categories in symptomatic adult patients of COVID-19 due to very small sized trial, clinically hydroxychloroquine+ribavirin therapy is showing better recovery by 7.4% than standard therapy in the former category. However, results do indicate the benefit of standard therapy in the non-severe category by 6.6%. Furthermore, the dose of ribavirin needs to be reconsidered in the Indian population.

Objective: This study was aimed to analyze the prescription pattern of disease modifying anti-rheumatic drug (DMARD) therapy in patients with rheumatoid arthritis (RA) in a tertiary care teaching hospital in Uttarakhand, India. Methodology: This cross-sectional study was conducted in 150 RA patients who were given DMARD therapy. Patient's demographic details, drugs prescribed with their dosage and administration routes and the usage of complementary and alternative medicine (CAM) therapy were recorded to study the prescription pattern. Results: Overall, 4 DMARDs were prescribed in all the studied patients: Methotrexate ( n = 150), hydroxychloroquine ( n = 35), leflunomide ( n = 5), and adalimumab ( n = 1). Single DMARD therapy with methotrexate was prescribed to 110 (73.3%) followed by double therapy with methotrexate + hydroxychloroquine in 35 (23.3%), triple therapy (methotrexate + hydroxychloroquine + leflunomide) in 4 (2.7%) and triple therapy with biological DMARD (methotrexate + hydroxychloroquine + leflunomide + adalimumab) in 1 (0.7%) patient. Adjuvant therapy drugs included: Prednisolone ( n = 150), folic acid ( n = 150), naproxen ( n = 150), calcium ( n = 150), vitamin D ( n = 150) and indomethacin ( n = 40). Of the total, 61.4% patients also took complimentary alternative medicine (CAM) therapy. Conclusion: Our study concludes that the most commonly prescribed DMARDs in our setting, to patients of RA, in descending order of frequency were methotrexate, followed by hydroxychloroquine, leflunomide and lastly adalimumab. A total of five adjuvant medications were commonly prescribed to all patients. There was a high prevalence of self-medicated CAM therapy in the majority of these patients.

This study was conducted with the aim of evaluating the cost-effectiveness of and adherence to treatment in patients on disease-modifying antirheumatic drug (DMARD) therapy for rheumatoid arthritis (RA) in a tertiary care teaching hospital in Uttarakhand, India. MethodologyThis prospective observational study was conducted on 150 rheumatoid arthritis patients presenting to the Rheumatology Outpatient Department (OPD) receiving DMARD therapy (approval number AIIMS/IEC/18/160). The patients were followed up for an average of 10.7 weeks and received drugs in four regimens with methotrexate (MTX) (Regimen 1) having the least contribution with a mean of 46.05 Rs, methotrexate + hydroxychloroquine (MTX + HCQ) (Regimen 2) with 174.15 Rs, methotrexate + hydroxychloroquine + leflunomide (MTX + HCQ + Lef) (Regimen 3) with Rs 371.70, and methotrexate + hydroxychloroquine + leflunomide + biological DMARD adalimumab (MTX + HCQ + Lef + bDMARD adalimumab) (Regimen 4) with 17,349.4 Rs. The cost of drug therapy was assessed by calculating the cost of therapy per month for each patient, and adherence was assessed using the Morisky-Green-Levine Scale (MGLS) at the follow-up visit. ResultsThe overall mean cost of DMARD treatment was 205.81 Rs. The overall DMARD therapy cost-effectiveness was Rs 878.14 for a unit change of Disease Activity Score (DAS28). The most cost-effective treatment came out to be Regimen 1 with the least cost of 290.9 Rs for a unit change of DAS28, and the least cost-effective was Regimen 4 with 65,661.8 Rs for a unit change of DAS28. At follow-up, among all subjects of the study, 49 (32.7%) subjects showed high adherence, 71 (47.3%) subjects showed medium adherence, and 30 (20%) subjects showed low adherence. Accordingly, the maximum number of participants fell in the category of medium adherence, i.e., 71 (47.4%). ConclusionOur study concluded that the cost burden varied according to the number of DMARDs being given to the patient. The double-drug therapy of methotrexate + hydroxychloroquine had a maximum "high adherence." On a whole, the majority of patients had "medium adherence" to therapy.

Background:Methotrexate (MTX) intolerance refers to unpleasant symptoms that accompany use of MTX and may lead to its discontinuation. However, it lacks a validated score in RA patients; with the only option being to use the MISS score which was validated for use in children and not adults.Objectives:To develop and validate a questionnaire and score (s) for measuring MTX intolerance and its severity in rheumatoid arthritis.Methods:A 10-item questionnaire called ‘Methotrexate Intolerance and Severity assessment in Adults’ (MISA) was validated in 105 RA patients. A score was calculated by adding the scores of first 7 questions (0 to 3 based on severity on symptoms), to last 3 questions (0 or 1); it ranged from 0 to 24 (MISA score) and was assessed for correctly classifying MTX intolerance (compared to an interview) by ROC analysis. Its area-under-curve (AUC) was compared with ‘Methotrexate Intolerance Severity Score’ (MISS), developed for children. Subsequently, it was administered to 414 RA patients to assess the prevalence and associations of MTX intolerance. In addition, the MISA cross-products score, that was calculated by adding the cross-products (severity (1 to 3) x duration per week (0.5 to 7 days)) of symptoms, was compared to MISA and MISS for assessing severity of intolerance.Results:In the initial phase, 105 RA patients on MTX≥6 months were included, a majority were female (87%), mean age was 51 (13.4) years and methotrexate dose was 18.8±6 mg/week. Thirty-five (33%) were found to be intolerant to MTX based on interview. MISA score had a good predictive ability (AUC of 0.904), to correctly classify MTX intolerance, and was better than MISS score (AUC of 0.823) (Figure 1A). The optimal cut-off for MISA was ≥1, with a sensitivity and specificity of 91.4% and 84.3%. Using the MISA score (≥1), 38.4% of 414 RA patients were found to have MTX intolerance: with nausea, lethargy and irritability being common symptoms. (Figure 1B, C) On multivariable analysis, age (OR 0.972) and BMI (OR 1.061) were significant predictors of MTX intolerance. (Table 1) On assessing for severity of intolerance, MISA cross product score performed the best, with an area-under-curve of 0.899 (95% CI 0.831-0.966), being higher than AUC for MISS and MISA score which were 0.847 (95% CI 0.768-0.927) and 0.837 (95% CI 0.754-0.920).Conclusion:MISA is the first validated questionnaire for assessing methotrexate intolerance in rheumatoid arthritis, with the MISA score having a good accuracy (at cut-off ≥1), to detect MTX intolerance. Methotrexate intolerance was present in more than one-third of RA patients, with nausea, lethargy and irritability being most common.Table 1.Baseline characteristics of 414 RA patients.VariableAll(n=414)Tolerant(n=255)Intolerant(n=159)p-valuetol. vs ntol.P-valuemultivariablemodelFemales, n (%)370 (89)231 (91)139 (87)0.31Age, yrs, mean (SD)50 (12.5)51.2 (12.6)48.2 (12.2)0.016*0.008**Duration of RA, yrs, mean (SD)10.0 (7.0)10.8 (7.4)9.6 (6.3)0.168BMI, Kg/m2a, mean (SD)24.0 (4.9)23.6 (4.9)24.6 (4.7)0.1070.03*RF positiveb, n (%)300 (73)191 (82)109 (78)0.29CDAI, mean (±SD)14.0 (11.8)14 (12.1)14.1 (11.4)0.69Dose of MTX, mg/wk, mean (SD)18.6 (5.6)18.6 (5.5)18.7 (5.8)0.83Injectable MTX, n (%)47 (11)25 (10)22 (14)0.21Use of FA, n (%)395 (95)241 (95)154 (97)0.27Use of other DMARD, n (%)272 (66)160 (62)112 (70)0.11HCQ n (%)209 (51)123 (48)86 (54)0.25Prednisolone n (%)156 (38)87 (34)69 (43)0.0580.21Using antiemetics, n (%)12 (3)1 (0.5)11 (7)<0.001a Available for 262 patients bAvailable for 372 patientsFigure 1.Figure showing the ROC curve for MISA and MISS questionnaires for MTX intolerance (A), Bar diagram showing the prevalence of various symptoms of intolerance in 414 RA patients (B), and Box-and-whiskers plot showing the duration of unpleasant symptoms (C).Disclosure of Interests:None declared